Details of the Drug Combination

General Information of Drug Combination (ID: DCWJ6CN)

Drug Combination Name
Buparlisib Everolimus
Indication
Disease Entry Status REF
Solid Tumors Phase 1 [1]
Component Drugs Buparlisib   DM1WEHC Everolimus   DM8X2EH
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Buparlisib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 3 [2]
Buparlisib Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase beta (PIK3CB) TTTHBCA PK3CB_HUMAN Inhibitor [8]
PI3-kinase delta (PIK3CD) TTGBPJE PK3CD_HUMAN Inhibitor [8]
PI3-kinase alpha (PIK3CA) TTEUNMR PK3CA_HUMAN Inhibitor [8]
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Inhibitor [8]
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Buparlisib Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Telomerase reverse transcriptase (TERT) OT085VVA TERT_HUMAN Decreases Expression [7]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [9]
Forkhead box protein O3 (FOXO3) OTHXQG4P FOXO3_HUMAN Increases Expression [9]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [10]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [7]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Increases Phosphorylation [10]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [10]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Increases Phosphorylation [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [7]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [10]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [11]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [7]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [7]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Expression [7]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [7]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) OTAYZMOY SIR1_HUMAN Decreases Expression [7]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Response To Substance [12]
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⏷ Show the Full List of 18 DOT(s)
Indication(s) of Everolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [3]
Advanced/metastatic breast cancer 2C60 Approved [4]
Brainstem neoplasm N.A. Approved [3]
Breast carcinoma N.A. Approved [3]
Graft-versus-host disease 4B24 Approved [3]
Intracranial meningioma N.A. Approved [3]
Leukemia N.A. Approved [3]
Lung cancer 2C25.0 Approved [3]
Mucosal melanoma N.A. Approved [3]
Multiple sclerosis 8A40 Approved [3]
Plasma cell myeloma 2A83.1 Approved [3]
Prostate cancer 2C82.0 Approved [3]
Renal cell carcinoma 2C90 Approved [5]
Salivary gland squamous cell carcinoma N.A. Approved [3]
Tuberous sclerosis LD2D.2 Approved [3]
Kidney cancer 2C90.0 Phase 3 [5]
Castration-resistant prostate carcinoma N.A. Investigative [3]
Colon cancer 2B90.Z Investigative [3]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [6]
Neuroblastoma 2D11.2 Investigative [3]
Pancreatic acinar cell carcinoma N.A. Investigative [3]
Polycystic kidney disease GB8Y Investigative [3]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [6]
Everolimus Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [13]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [6]
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Everolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [14]
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Everolimus Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [15]
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References

1 ClinicalTrials.gov (NCT01470209) A Phase I Study of BKM120 and Everolimus in Advanced Solid Malignancies
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7878).
3 Everolimus FDA Label
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5889).
6 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
7 Inhibition of PI3K signaling pathway enhances the chemosensitivity of APL cells to ATO: Proposing novel therapeutic potential for BKM120. Eur J Pharmacol. 2018 Dec 15;841:10-18. doi: 10.1016/j.ejphar.2018.10.007. Epub 2018 Oct 11.
8 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
9 Inhibition of PI3K pathway using BKM120 intensified the chemo-sensitivity of breast cancer cells to arsenic trioxide (ATO). Int J Biochem Cell Biol. 2019 Nov;116:105615. doi: 10.1016/j.biocel.2019.105615. Epub 2019 Sep 17.
10 Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer. Cancer Lett. 2014 Jun 1;347(2):204-11. doi: 10.1016/j.canlet.2014.02.018. Epub 2014 Feb 24.
11 The dual PI3K/mTOR inhibitor NVP-BEZ235 and chloroquine synergize to trigger apoptosis via mitochondrial-lysosomal cross-talk. Int J Cancer. 2013 Jun 1;132(11):2682-93. doi: 10.1002/ijc.27935. Epub 2012 Dec 4.
12 Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations. Mol Cancer Ther. 2012 Aug;11(8):1747-57. doi: 10.1158/1535-7163.MCT-11-1021. Epub 2012 May 31.
13 Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
14 Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
15 The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.